1. Field of the Invention
The invention relates to a compound which, through biological signals towards lymphocytes, induces development and maturation of lymphocytes and method to control the cytotoxic enhancement of lymphocytes in the intestine. The invention can be used as a therapeutic method to modulate immune responses in the prevention and treatment of a broad variety of disorders including infections and cancers.
2. Description of the Related Art
Epidemiological studies have provided evidence that dietary components in food influence the development of illnesses, e.g., infections and cancers, in human populations. The immune system combines several different strategies in dealing with abnormal cells (cancer) or foreign organisms (viruses, bacteria, parasites). Exposure of blood cells to foreign or abnormal molecules (antigens) stimulates the growth of specialized white cells (B lymphocytes) which produce antibodies. These circulate in the blood or concentrate at mucosal surfaces such as the lungs, the nose, and the intestines, which are prime entry points for invading organisms. The antibodies recognize and bind with high specificity to their target, marking it out for disposal by the scavenger cells of the body. Even in the absence of a specific immune response, these scavenger cells play an important role in body defenses. Phagocytes and natural killer cells recognize and destroy cancer cells, viruses, and parasites as well as stimulate other components of the immune system. An important aspect of long-term immunity is stimulation of other white cells (T lymphocytes) by antigens. The T cells produce cytokines which increase the effectiveness of scavenger cells. At the same time, the scavenger cells take up antigens and display fragments of these foreign proteins of their surfaces, increasing T cell stimulation.
The intestinal mucosal immune system is adapted to protect the host against potential pathogens. Thus, a complex population of T lymphocytes can be found in the gut-associated lymphoid tissues (GALTs). Lymphocytes are localized in the Peyer""s patches, the lymphoid follicles in the colonic mucosa, in the intestinal lamina propria, and above the basement membrane between epithelial cells, i.e., they are lamina propria lymphocytes (LPLs) and intraepithelial lymphocytes (IELs). More than 95 percent of human LPLs have the alpha/beta isotype of the antigen-specific T-cell receptor (TCR). Additionally, CD4- and CD8-positive T cells are present in the laminapropria and in the peripheral blood in a similar proportion. Usually, immature precursors of T lymphocytes from haematopoietic sources are matured in the thymus, i.e., genes that encode the alpha- and beta-chains of their receptors are rearranged. However, extrathymic T cells which differentiate in the intestines or the liver seems to stand at an intermediate position between natural killer (NK) cells and thymus-derived T cells in the phylogenetic development. The ability of the intestine to induce development and maturation of extrathymic T cells, e.g., LPLs and IELS, makes phylogenetic sense. From an evolutionary point of view, GLATs constitute the first distinct lymphoid tissues in vertebrates, appearing prior to the spleen, the thymus, the bone marrow, and the lymph nodes.
Extrathymic T cells play a role in (a) aging, (2) conditions of malignancy at tumor sites, (3) intracellular infections, (4) pregnancy, (5) autoimmune diseases, and (6) elimination of abnormal self-cells generated by the body itself. Pathways of T cells may increase, accompanying acute thymic atrophy. Intestinal epithelium may induce IEL development without the action of thymic-derived products, or a thymus may promote extrathymic development processes either directly or indirectly. Recent findings give empirical evidence that alternative mechanisms exist for rendering IELs tolerant of normal host tissues. Thus the intestinal epithelium has an intricate and well-refined process for the elimination of autoreactive T cells in a thymus-independent manner.
Pectins are soluble dietary fibers, which are completely metabolized in the gut due to bacterial fermentation. Pectin is a complex mixture of colloidal polysaccharides found in the primary cell walls of dicotyledons (dicots). In vitro test has demonstrated that several polysaccharides contained in pectin have immune stimulating actions. Rhamnogalacturonan enhance the cytotoxic activity of human natural killer (NK) cells and T cells, arabinogalactan activate macrophage and reduce or inhibit metastasis.
In 1994, an in vivo experiment was designed in Michigan by Avraham Raz, Kenneth Pienta, and coworkers. Laboratory animals were fed with citrus pectins in the drinking water. The purpose was to see if pectic polysaccharides influenced primary tumor growth and metastasis. Male Copenhagen rats had fast-growing, prostate adenocarcinoma cells injected into their thigh. This resulted in death of control animals within approximately 25 days. However, if the primary tumor was removed before metastasis after about 10 days, control animals could be saved from dying. Interestingly, rats consuming 1.0 percent w/v citrus pectins per day from day four showed a significant reduction in spontaneous lung metastases. Additionally, a significant reduction in the average frequency of metastases per lung was observed. This work was reported in an article by Pienta et al., xe2x80x9cInhibition of Spontaneous Metastasis in a Rat Prostate Cancer Model by Oral Administration of Modified Citrus Pectin,xe2x80x9d Journal of the National Cancer Institute, Vol. 87, No. 5, Mar. 1, 1995.
The compound comprises the protein extensin or a combination of (1) pectin or polysaccharides found in the pectic molecule and (2) extensin.
The invention relates to a method for using extensin or a combination of pectin or polysaccharides found in the pectic molecule and extensin which is beneficial to health because it can enhance the activity of the immune system.
The invention also relates to a method for preparing a therapeutically effective pharmaceutical for the cytotoxic enhancement of lymphocytes.